We have been DOCKing combinatorial libraries to potential protein targets to determine the optimal library for a given target as well as alternative targets for a given library. For proof-of-concept, we are applying this approach to the serine, cysteine, and aspartyl proteases. The initial goal is to reproduce known subsite side chain specificities for the proteases, especially that of the S1 pocket of serine proteases. In addition, the subsites of the proteases have been characterized with a surface normal vector representation and used to rank scaffold orientations. Molecular surfaces calculated using the dms program and visualized using MidasPlus are key in this effort. In the future, we will address whether family-specific or member-specific subsite representations are useful for library enrichment.